Antinuclear factors in rheumatoid arthritis. Increasing organ-non-specificity with increasing reactivity of rheumatoid factor with heterologous gamma globulin.

McCormick and Day (1963) reported that rheumatoid factors and 7S ANF co-existing in the same seramayform high molecular weight complexes, and absorption studies have brought forward evidence of an interaction between ANF and rheumatoid factors when present in the same serum (Holborow and Johnson, 1965). However, ANF in rheumatoid arthritis have mostly been found in low frequency and chiefly in the 19S gamma globulin fraction (Weir and Holborow, 1962; Baum and Ziff, 1962); as emphasized by Baum and Ziff (1962) such gamma globulin cannot be the 7S substrate required for rheumatoid factors. It has recently been shown, however, that a high proportion of sera and synovial fluids from patients with definite rheumatoid arthritis may contain IgG ANF, which reacts exclusively with a DNAse sensitive antigen localized in nuclei of (polymorphonuclear) granulocytes (Elling, 1967; Elling, Graudal, and Faber, 1967, 1968). The limited nuclear reactivity of this antinuclear antibody may suggest that its production is caused by an immunization with nuclear material derived from polymorphs rather than from bacteria or virus. The presence of granulocyte-specific ANF in synovial fluids and not in corresponding sera in some cases may also suggest that the nuclear material is derived from polymorphs involved in the arthritic inflammation (Elling and others, 1968). In clinical material, highly controversial results have appeared concerning the relationship between rheumatoid factors and ANF. Since these variations may be caused by the existence of ANF with limited nuclear reactivity, the present investigation into the relationship between these factors was performed with special emphasis on the correlation between ANF with monospecificities or multispecificities and the two main groups of rheumatoid